Syringes already filled with an aqueous-based drug solution play an increasingly important role in the pharmaceutical industry and the medical community. For the purposes of this invention, such filled syringes are defined to as post-filled syringes; i.e., post/after the time of filling the syringe with the solution, which is in contrast to pre-filled, which is defined for the purposes of this invention to as prior/before the time of filling the syringe with the solution.
Within the industry community, post-filled syringes represent a market share of over $2 billion dollars, with over 60 products on the market and a growing number of protein-based products expected to enter the market in the near future.
From a medical standpoint, post-filled syringes allow for improved drug delivery that is less wasteful, safer, and frequently easy enough for patients to do without the oversight of a medical professional.
An important part of the syringe is the plunger system, which relies on a layer of lubricant to allow for ideal glide force and ensuring complete delivery of the drug product.
The most common lubricant is silicone-based oil, and the siliconization of these syringes, understandably has played an important part in the development of pre-filled syringes. As well as providing an ideal glide force and ensuring that the plunger travels the full path, siliconization also provides several advantages. It is a hydrophobic oil allowing for easy emptying of a drug product, and the oil is low reacting, frequently used as a buffer layer between the syringe barrel and the drug product ensuring no reaction takes place between the two materials.
This has led to the use of siliconization in other applications beyond the post-filled syringe market, such as use as coating in vials and ampules in some cases. Siliconization is a widely used process that has been often overlooked and under-championed, despite its use, and manufacturing concerns over proper siliconization and the demands for testing to determine uniform coverage have often gone overlooked. An example of this is the Amgen recall of 2006 in Europe, requiring millions of drug product to be returned as improper siliconization was to blame for improper dosing.
As important as this process is, several manufacturing concerns are still being dealt with to-date. Too much silicone oil can lead to protein aggregation and too little oil can be telling of an improper spraying within the manufacturing environment. Protein aggregation has the potential to produce improper antibodies within the drug that on delivery could cause an unwanted, potentially fatal response in a human. In systems with agitation, the protein build-up is significant enough to be observed visually with the naked eye. Also, large amounts of sprayed oil have led to oil droplets within the drug product.
For sensitive applications, such as injections into the human eye for treatment, silicone oil droplets are observable within patients with an unknown amount of damage. As the FDA and other governing bodies work to not only establish the danger of these and other leachables, it is important to develop technology that will allow the greatest amount of quality control over the manufacturing process. The only way to guarantee high-quality coatings being delivered is through 100%, high-speed inspection of pre-filled and/or post-filled syringes, which is the topic of this invention.